Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix
OPEN ACCESS
Loading...
Author / Producer
Date
2018-04-13
Publication Type
Journal Article, Journal Article
ETH Bibliography
no
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
Aurora‐A regulates the recruitment of TACC3 to the mitotic spindle through a phospho‐dependent interaction with clathrin heavy chain (CHC). Here, we describe the structural basis of these interactions, mediated by three motifs in a disordered region of TACC3. A hydrophobic docking motif binds to a previously uncharacterized pocket on Aurora‐A that is blocked in most kinases. Abrogation of the docking motif causes a delay in late mitosis, consistent with the cellular distribution of Aurora‐A complexes. Phosphorylation of Ser558 engages a conformational switch in a second motif from a disordered state, needed to bind the kinase active site, into a helical conformation. The helix extends into a third, adjacent motif that is recognized by a helical‐repeat region of CHC, not a recognized phospho‐reader domain. This potentially widespread mechanism of phospho‐recognition provides greater flexibility to tune the molecular details of the interaction than canonical recognition motifs that are dominated by phosphate binding.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
37 (8)
Pages / Article No.
Publisher
EMBO Press
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Disorder-order transition; Intrinsically disordered proteins; Phosphorylation; Protein kinase; Protein-protein interaction
Organisational unit
03602 - Panke, Sven / Panke, Sven